Natural products have shown significant therapeutic potential and are increasingly considered for clinical use in prevention, diagnosis, and treatment. Compared to synthetic drugs, natural products have diverse structures and exhibit various biological activities against different diseases, making them attractive for drug development. However, challenges such as poor solubility, limited stability, and short duration of action hinder their full potential. Nano-drug delivery systems have emerged as a promising solution to overcome these barriers, offering advantages like large surface area, enhanced targeting, and controlled release. Extensive studies have demonstrated the efficacy and safety of nanoparticle-based systems in delivering natural products in preclinical models. This review discusses the limitations of natural products and their current status with nanotechnology, focusing on three aspects: targeting warheads, self-assembly, and co-delivery. It also addresses challenges in clinical translation of nano-drugs. Natural products, including terpenoids, flavonoids, polyphenols, and alkaloids, have been studied for their potential in drug delivery. Nano-carriers such as liposomes, micelles, and nanoparticles have been developed to enhance solubility, stability, and targeted delivery of these compounds. For example, triptolide and ginsenoside have been delivered using nano-carriers to improve bioavailability and therapeutic effects. Flavonoids like gambogic acid and baicalin have been delivered using targeted nano-carriers to enhance their efficacy. Polyphenols such as resveratrol and curcumin have been delivered using nano-carriers to improve their stability and bioavailability. Alkaloids like paclitaxel have been delivered using nano-carriers to enhance their solubility and targeting. Self-assembly techniques have been used to develop nano-drug delivery systems, offering advantages such as low cost, low energy consumption, and improved drug solubility and targeting. Peptide-based nano-drug delivery systems have shown promise in enhancing drug delivery efficiency and reducing toxicity. Metal-coordinated polyphenol nanonetworks have also been developed for drug delivery, demonstrating potential in cancer therapy. These advancements highlight the potential of nano-drug delivery systems in improving the clinical application of natural products.Natural products have shown significant therapeutic potential and are increasingly considered for clinical use in prevention, diagnosis, and treatment. Compared to synthetic drugs, natural products have diverse structures and exhibit various biological activities against different diseases, making them attractive for drug development. However, challenges such as poor solubility, limited stability, and short duration of action hinder their full potential. Nano-drug delivery systems have emerged as a promising solution to overcome these barriers, offering advantages like large surface area, enhanced targeting, and controlled release. Extensive studies have demonstrated the efficacy and safety of nanoparticle-based systems in delivering natural products in preclinical models. This review discusses the limitations of natural products and their current status with nanotechnology, focusing on three aspects: targeting warheads, self-assembly, and co-delivery. It also addresses challenges in clinical translation of nano-drugs. Natural products, including terpenoids, flavonoids, polyphenols, and alkaloids, have been studied for their potential in drug delivery. Nano-carriers such as liposomes, micelles, and nanoparticles have been developed to enhance solubility, stability, and targeted delivery of these compounds. For example, triptolide and ginsenoside have been delivered using nano-carriers to improve bioavailability and therapeutic effects. Flavonoids like gambogic acid and baicalin have been delivered using targeted nano-carriers to enhance their efficacy. Polyphenols such as resveratrol and curcumin have been delivered using nano-carriers to improve their stability and bioavailability. Alkaloids like paclitaxel have been delivered using nano-carriers to enhance their solubility and targeting. Self-assembly techniques have been used to develop nano-drug delivery systems, offering advantages such as low cost, low energy consumption, and improved drug solubility and targeting. Peptide-based nano-drug delivery systems have shown promise in enhancing drug delivery efficiency and reducing toxicity. Metal-coordinated polyphenol nanonetworks have also been developed for drug delivery, demonstrating potential in cancer therapy. These advancements highlight the potential of nano-drug delivery systems in improving the clinical application of natural products.